Sucrose and saccharin differentially modulate depression and anxiety-like behavior in diabetic mice: exposures and withdrawal effects

Rationale Sugar has addictive potential owing to increase in monoaminergic-transmission at pleasure and reward centers of brain. Insulin dysfunction triggered synaptic monoamine deficit is associated with sugar overeating and craving-related psychological changes in diabetic patients. Sugar-substitute (saccharin) is non-caloric artificial sweetener that may alleviate brain disorders in diabetes. Objectives In present study, effects of sucrose and sugar-substitute (saccharin) exposures and withdrawal on depression and anxiety-like behavior in type 2 diabetic mice were assessed. Methods Swiss albino mice were injected with streptozotocin (135 mg/kg). After induction of diabetes, mice were exposed to a two-bottle water-water, 10% sucrose-water, or 10% saccharin-water choice paradigm for 28 days. Separate groups were employed to assess withdrawal effect of sucrose or saccharin in diabetic mice. Monoamine oxidase (MAO), corticosterone, thiobarbituric acid reactive substances (TBARS), and reduced glutathione (GSH) were quantified after behavioral tests. Results Diabetic mice manifested preference towards 10% sucrose or saccharin over water. Sucrose-overeating by diabetic mice amplified symptoms of depression and anxiety; however, withdrawal further exaggerated these behavioral abnormalities. Substitution of sucrose by 10% saccharin attenuated the depressive and anxiety-like behavior in comparison to diabetic mice that were exposed separately to water-water or sucrose-water alone, and with respect to normal mice. Although withdrawal from saccharin resurfaced behavioral anomalies in diabetic mice, however, these were significantly low in comparison with withdrawal from sucrose or normal group. Reinstatement of exposure to saccharin mitigated symptoms of depression and anxiety in diabetic mice. Conclusion Preference of sucrose overeating augments while saccharin mitigates depressive and anxiety behavior during diabetes.